CoChat
Sign Up
Cited by 2Pneumonia and Respiratory InfectionsAntibiotic Resistance in BacteriaRespiratory viral infections research

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Impact of respiratory syncytial virus on Streptococcus pneumoniae resistance to β-lactam antibiotics: an investigative study in children

Open access
Li, Lu, Wan, Yushun, Wang, Yuncheng, Tao, Ye, Long, Xiao, Liu, Enmei, Deng, Yu·2025·BMC Microbiology
DOI 10.1186/s12866-025-04066-5PMC PMC12147270

Published version of a preprint

Open this paper in CoChat — free accountOpen PDF

Abstract

BACKGROUND: This study characterizes the molecular interplay between respiratory syncytial virus (RSV) glycoproteins (G/F) and Streptococcus pneumoniae (S.pn) penicillin-binding proteins (PBPs), while evaluating RSV's potential role in modulating S.pn β-lactam resistance. METHODS: Protein docking and pull-down assays assessed G/F-PBP interactions. In vitro RSV-S.pn co-culture experiments evaluated β-lactam susceptibility (MIC determination). We retrospectively analyzed 2012-2021 antimicrobial resistance data from 1-59-month-old community-acquired pneumonia patients at Chongqing Medical University Children's Hospital with confirmed S.pn and/or RSV nasopharyngeal carriage. RESULTS: Computational modeling revealed low G/F-PBP binding affinity (iPTM < 0.6), corroborated by absent PBP1a interaction in pull-down assays. RSV exposure did not alter S.pn β-lactam MICs (penicillin/amoxicillin ≤ 2 µg/mL; cefepime/cefotaxime ≤ 1 µg/mL; meropenem ≤ 0.25 µg/mL). Retrospective data showed elevated penicillin resistance in RSV + S.pn co-detections vs. S.pn alone during 2012 (2.8% vs. 40.9%), 2017 (2.8% vs. 30.4%), and 2018 (6.2% vs. 38.6%) (all p < 0.001). No RSV-associated resistance increases occurred for amoxicillin, cephalosporins, or meropenem. CONCLUSIONS: RSV demonstrates negligible impact on S.pn β-lactam resistance mechanisms, elevated resistance rates to amoxicillin and cephalosporins necessitate enhanced antimicrobial stewardship through diagnostic-guided prescribing and resistance surveillance to optimize β-lactam efficacy in pediatric care.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1186/s12866-025-04066-5

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Show all 1 references

Research works printed but not linked: 31

  1. Wada FW, Desta AF, Gebre M, Mihret W, Seyoum T, Melaku K, et al. Pneumococcal colonization and coinfecting respiratory viruses in children under 5 years in addis Ababa, Ethiopia: a prospective case-control study. Sci Rep. 2024;14(1):4174. · DOI
  2. Liu YN, Zhang YF, Xu Q, Qiu Y, Lu QB, Wang T, et al. Infection and co-infection patterns of community-acquired pneumonia in patients of different ages in China from 2009 to 2020: a National surveillance study. Lancet Microbe. 2023;4(5):e330–9. · DOI
  3. Diaz-Diaz A, Bunsow E, Garcia-Maurino C, Moore-Clingenpeel M, Naples J, Juergensen A, et al. Nasopharyngeal codetection of Haemophilus influenzae and Streptococcus pneumoniae shapes respiratory syncytial virus disease outcomes in children. J Infect Dis. 2022;225(5):912–23. · DOI
  4. de Steenhuijsen Piters WA, Heinonen S, Hasrat R, Bunsow E, Smith B, Suarez-Arrabal MC, et al. Nasopharyngeal microbiota, host transcriptome, and disease severity in children with respiratory syncytial virus infection. Am J Respir Crit Care Med. 2016;194(9):1104–15. · DOI
  5. Smith AM. Quantifying the therapeutic requirements and potential for combination therapy to prevent bacterial coinfection during influenza. J Pharmacokinet Pharmacodyn. 2017;44(2):81–93. · DOI
  6. Zapun A, Contreras-Martel C, Vernet T. Penicillin-binding proteins and beta-lactam resistance. FEMS Microbiol Rev. 2008;32(2):361–85. · DOI
  7. Sauvage E, Kerff F, Terrak M, Ayala JA, Charlier P. The penicillin-binding proteins: structure and role in peptidoglycan biosynthesis. FEMS Microbiol Rev. 2008;32(2):234–58. · DOI
  8. Behmard E, Najafi A, Ahmadi A. Understanding the resistance mechanism of penicillin binding protein 1a mutant against cefotaxime using molecular dynamic simulation. J Biomol Struct Dyn. 2019;37(3):741–9. · DOI
  9. Boccalini S, Bonito B, Salvati C, Del Riccio M, Stancanelli E, Bruschi M et al. Human respiratory syncytial virus epidemiological burden in pediatric outpatients in Italy: A systematic review. Vaccines (Basel). 2023;11(9). · DOI
  10. Amodio E, Belluzzo M, Genovese D, Palermo M, Pisciotta V, Vitale F. What ‘case definition’ for respiratory syncytial virus infection? Results of a systematic literature review to improve surveillance among the adults. J Public Health (Oxf). 2024. · DOI
  11. Smith CM, Sandrini S, Datta S, Freestone P, Shafeeq S, Radhakrishnan P, et al. Respiratory syncytial virus increases the virulence of Streptococcus pneumoniae by binding to penicillin binding protein 1a. A new paradigm in respiratory infection. Am J Respir Crit Care Med. 2014;190(2):196–207. · DOI
  12. Liu JR, Zhao CS, Zhao SY. Interpretation of the norms for the diagnosis and treatment of children’s community-acquired pneumonia 2019. Chin J Practical Pediatr. 2020;35(03):185–7. (Text by Chinese).
  13. Jawad B, Adhikari P, Podgornik R, Ching WY. Key interacting residues between RBD of SARS-CoV-2 and ACE2 receptor: combination of molecular dynamics simulation and density functional calculation. J Chem Inf Model. 2021;61(9):4425–41. · DOI
  14. O’Daniel PI, Peng Z, Pi H, Testero SA, Ding D, Spink E, et al. Discovery of a new class of non-β-lactam inhibitors of penicillin-binding proteins with Gram-positive antibacterial activity. J Am Chem Soc. 2014;136(9):3664–72. · DOI
  15. Griffiths C, Drews SJ, Marchant DJ. Respiratory syncytial virus: infection, detection, and new options for prevention and treatment. Clin Microbiol Rev. 2017;30(1):277–319. · DOI
  16. Li L, Ma J, Yu Z, Li M, Zhang W, Sun H. Epidemiological characteristics and antibiotic resistance mechanisms of Streptococcus pneumoniae: an updated review. Microbiol Res. 2023;266:127221. · DOI
  17. Lupoli TJ, Lebar MD, Markovski M, Bernhardt T, Kahne D, Walker S. Lipoprotein activators stimulate Escherichia coli penicillin-binding proteins by different mechanisms. J Am Chem Soc. 2014;136(1):52–5. · DOI
  18. Hakenbeck R, Brückner R, Denapaite D, Maurer P. Molecular mechanisms of β-lactam resistance in Streptococcus pneumoniae. Future Microbiol. 2012;7(3):395–410. · DOI · Paper page
  19. Muñoz R, Dowson CG, Daniels M, Coffey TJ, Martin C, Hakenbeck R, et al. Genetics of resistance to third-generation cephalosporins in clinical isolates of Streptococcus pneumoniae. Mol Microbiol. 1992;6(17):2461–5. · DOI
  20. Chen YY, Hsieh YC, Gong YN, Liao WC, Li SW, Chang IY, et al. Genomic insight into the spread of Meropenem-Resistant Streptococcus pneumoniae Spain(23F)-ST81, Taiwan. Emerg Infect Dis. 2020;26(4):711–20. · DOI
  21. Li Y, Metcalf BJ, Chochua S, Li Z, Gertz RE Jr., Walker H et al. Penicillin-Binding protein transpeptidase signatures for tracking and predicting β-Lactam resistance levels in Streptococcus pneumoniae. mBio. 2016;7(3). · DOI
  22. Negash AA, Asrat D, Abebe W, Aseffa A, Vaneechoutte M. Phenotypic and molecular characterization of penicillin and Macrolide-Resistant Streptococcus pneumoniae serotypes among pediatric patients in addis Ababa, Ethiopia. Infect Drug Resist. 2021;14:1765–72. · DOI
  23. Zhou M, Wang Z, Zhang L, Kudinha T, An H, Qian C, et al. Serotype distribution, antimicrobial susceptibility, multilocus sequencing type and virulence of invasive Streptococcus pneumoniae in China: A Six-Year multicenter study. Front Microbiol. 2021;12:798750. · DOI
  24. Zintgraff J, Gagetti P, Napoli D, Sanchez Eluchans N, Irazu L, Moscoloni M, et al. Invasive Streptococcus pneumoniae isolates from pediatric population in Argentina for the period 2006–2019. Temporal progression of serotypes distribution and antibiotic resistance. Vaccine. 2022;40(3):459–70. · DOI
  25. Luna PN, Hasegawa K, Ajami NJ, Espinola JA, Henke DM, Petrosino JF, et al. The association between anterior Nares and nasopharyngeal microbiota in infants hospitalized for bronchiolitis. Microbiome. 2018;6(1):2. · DOI
  26. García CG, Bhore R, Soriano-Fallas A, Trost M, Chason R, Ramilo O, et al. Risk factors in children hospitalized with RSV bronchiolitis versus non-RSV bronchiolitis. Pediatrics. 2010;126(6):e1453–60. · DOI
  27. Hament JM, Aerts PC, Fleer A, Van Dijk H, Harmsen T, Kimpen JL, et al. Enhanced adherence of Streptococcus pneumoniae to human epithelial cells infected with respiratory syncytial virus. Pediatr Res. 2004;55(6):972–8. · DOI
  28. Stacevičienė I, Petraitienė S, Vaičiūnienė D, Alasevičius T, Kirslienė J, Usonis V. Antibiotic resistance of Streptococcus pneumoniae, isolated from nasopharynx of preschool children with acute respiratory tract infection in Lithuania. BMC Infect Dis. 2016;16:216. · DOI
  29. Yao KH. Overview of the burden of Streptococcus pneumoniae diseases in China. Natl Med J China. 2020;100(42):3363–6. (Text by Chinese).
  30. Tsai HY, Lauderdale TL, Wang JT, Chen YS, Liu JW, Huang JH, et al. Updated antibiotic resistance and clinical spectrum of infections caused by Streptococcus pneumoniae in Taiwan: emphasis on risk factors for penicillin nonsusceptibilities. J Microbiol Immunol Infect. 2013;46(5):345–51. · DOI
  31. Klugman KP. Risk factors for antibiotic resistance in Streptococcus pneumoniae. S Afr Med J. 2007;97(11 Pt 3):1129–32.

Metadata

Authors
Li, L., Wan, Y., Wang, Y., Tao, Y., Long, X., Liu, E., & Deng, Y.
Affiliations
  • Children's Hospital of Chongqing Medical University (CN)
  • Chongqing Medical University (CN)
Corresponding author
  • Wan, Yushun
  • Liu, Enmei
  • Deng, Yu
ORCID
Venue
BMC Microbiology
Publisher
Springer Science and Business Media LLC
Published
2025-06-09
Volume
25
Issue
1
Pages
363-363
ISSN
1471-2180 (ISSN-L)
DOI
10.1186/s12866-025-04066-5
PMC
PMC12147270
OpenAlex
W4411131143
Cited by
2
References
1
Citations by year
2026: 2
FWCI
1.39
Type
journal article
Language
en
Open access
Licence
Locations
  • BMC Microbiology (publishedVersion, cc-by-nc-nd)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Four Major Chronic Diseases Initiative - Early-Career Researcher Development Program (2023ZD0517400)
  • National key Research and Development Program of China (2022YFC2704900)
  • Natural Science Foundation of Chongqing,China (cstc2019jycj-msxmX0858)
  • CQMU Program for Youth Innovation in Future Medicine
Topics
  • Health Sciences › Medicine › Epidemiology › Pneumonia and Respiratory Infections
  • Health Sciences › Medicine › Microbiology (medical) › Antibiotic Resistance in Bacteria
  • Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
Keywords
respiratory syncytial virus, Streptococcus pneumoniae, beta-lactam resistance, penicillin-binding proteins, protein-protein interaction, co-infection, community-acquired pneumonia, pediatric patients, antimicrobial resistance, cephalosporin resistance, amoxicillin resistance, antimicrobial stewardship
MeSH terms
beta Lactam Antibiotics, Anti-Bacterial Agents, Child, Preschool, Female, Humans, Infant, Male, Microbial Sensitivity Tests, Pneumococcal Infections, Retrospective Studies, Streptococcus pneumoniae, Community-Acquired Infections, Respiratory Syncytial Virus, Human, Respiratory Syncytial Virus Infections, beta-Lactam Resistance, Penicillin-Binding Proteins, beta-Lactams, Coinfection

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review